1. Field of the Invention
The present invention generally relates to an electrospinning manufacture for drug carriers and, more particularly, to an electrospinning manufacture for controlling the size and shape of produced drug carriers.
2. Description of the Related Art
In biotechnological manufacturing industry, due to the particular essential or function of the emerging protein drug, conventional drug transmission system may no longer be appropriate for drug delivery to individuals. (not be transmitted to a living body via conventional methods due to the special characteristics and effects thereof). Therefore, the development and application of the drug transmission system has become an important issue in recent decades. Mainly, the drug transmission system is designed to precisely control the function of a predetermined drug in right place and right time in order to reduce some predetermined side effects. (to an affected part so that the bioavailability of the predetermined drug is improved and the side effects of the predetermined drug are reduced.) Based on diverse requirements of technical platforms, the conventional drug carriers are mainly categorized into transplantation type, adhesion type and time-releasing type, as described below.
The transplantation-type drug carrier is mainly repairing or replacing the tissue damages of human body. The transplantation-type drug carrier is primarily from some natural or synthesized polymer such as collagen, chitosan, polyglycolide acid and so on. Generally, the polymers have biocompatibility and biodegradability which provide enough space for cell growth as implanted into human body. As disclosed in Taiwan Patent Number I283585a discloses a mixture containing bone cement powder, as well as tricalcium phosphate coated by chitosan particles, for facilitating regeneration of bone cells in order to improves the fixing effects and side effects of conventional bone powder.
The adhesion-type drug carrier is mainly for cell adhesion, with some synthesized materials including synthesized polyethylene, polyvinyl chloride and polymethacrylic acid resin manufactured as drug carriers especially for protein drugs. In this way, the cell growth and cell decomposition of the target part can be facilitated.
The time-releasing type drug carrier is primarily made form alginate. The alginate is a natural nonpoisonous polymer of polymeric saccharides belonging to unbranched polysaccharide. The alginate is capable to form colloids in a divalent cation agent to apply to various biological substances and medications, which subsequently performs at a coating behavior. For example, Taiwan Patent Number 524699 discloses a manufacturing method for producing a multi-ingredient particle of collagen and biochemical ceramic powder in which a mixture of a soluble collagen, a biomedicine ceramic powder and an alginate solution is dropped into a divalent cation agent to obtain some biological micromaterials via a cross-linking reaction between the mixture and the divalent cation agent.
On the other hand, the manufacturing method of conventional drug carriers is substantially categorized into dropping, emulsion and electrospinning. In the dropping method, a mixture of a predetermined drug and a polymer, such as alginate, is dropped into a cross-linked agent, such as a divalent cation agent in order to obtain particles of drug carrier via a crosslinking-gelating reaction between the mixture and the divalent cation agent. The particles of drug carrier obtained from the dropping method substantially have a diameter of 1.2 millimeter.
In the emulsion, a mixture of a polymer, a predetermined drug to be encapsulated, an emulsifier and a lipid is forced to pass through a hydrophobic membrane by a gaseous matter, so as to obtain emulsified drips. Sequentially, a cross-linked agent is added into the emulsified drips so that a crosslinking-gelating reaction of the polymer can be performed. In this situation, the particles may be dehydrated to obtain particle drug carriers with a diameter of about 200 millimeter. For instance, Taiwan Patent Number I301422 discloses a solidification process of the emulsion in which an emulsified solution and a solidification solution are prepared and injected into a Y-shaped crotched passageway to obtain drug carriers. In the solidification, the mixture of the emulsified solution and a solidification solution is preferably prepared in advance so as to shorten the reaction time period of solidification. In addition, smaller drug carriers are obtained by controlling the flow speed of the emulsified solution and a solidification solution in the Y-shaped crotched passageway.
However, since the above dropping and emulsion mechanisms produce the drug carriers in a random manner, the quantity and size of produced drug carriers are not easy to control. That is, the produced drug carriers tend to have different diameter and size. Therefore, the function and utility of the drug carriers can be interfered and unpredicted. Furthermore, the ratio of the ingredients and the manipulation steps must be accurately handled to ensure a desired process of the drug carriers. Therefore, longer manipulation time is required and the manufacturing process of the drug carriers tends to be affected by human factors. Therefore, the dropping and emulsion mechanisms are not suitable for industrial production in drug manufacturing industry.
The electrospinning technology is the emerging nanotechnology in recent years. It can rapidly and directly transform a polymer into a nanofiber usually in taper shape. The drug fibers are generally applied to surgical transplantations or for direct adhesion of wounded parts or for any other medical field. As an example, Taiwan Publication Number 200740472 discloses another nanofiber produced by electrospinning in which a mixture containing a fixed-ratio of a collagen, chitosan, polyethylene oxide and an acid solution is prepared and manufactured into nanofiber. The nanofiber may serve as a medical dressing for wounded parts which has better biocompatibility and larger surface area for facilitating the healing of the wounded parts.
However, the biomaterials produced by the electrospinning technology are only suitable for use in transplantation or in use as medical dressings due to the taper shape thereof. In other words, it is less efficient if applied to oral taking, inhaling or injection for treatments, thus limiting the use thereof.
Taiwan Patent Number I301415 discloses a nanometer-sized collagen produced by placing a collagen in a fluid environment with an electric field applied. The nanometer-sized collagen has a simpler manufacture process and is more easily to be absorbed by living bodies. Although the produced biomaterials are in particle form and easy to be absorbed by living bodies, they are used merely for cell regeneration. Therefore, the use thereof is still limited.
In recent years, more and more drug carriers are manufactured via electrospinning technology. During the manufacturing, a high-voltage electric field is applied to move a mixture of a predetermined drug and a chitosan liquor from a source to a cross-linking agent (which in generally is a salt liquor with metal ions), allowing the high polymer materials of the chitosan liquor to have a conjugation with the metal ions of the curing agent. In this way, the high polymer materials of the chitosan liquor may become a high polymer gel. Then, the predetermined drug is coated with the high polymer gel to form a particle drug carrier having a slow releasing function. Note the particle drug carrier is manufactured in a single step.
However, the particle drug carriers produced by the electrospinning have some drawbacks described below. Firstly, the particle drug carriers are manufactured via the interaction of the chitosan and the cross-linking agent. However, the chitosan stays positively charged only in an acid environment and may then be able to react with the electric field. Therefore, an acid liquor is required for melting the chitosan before the electrospinning technology is applied. However, the acid liquid has negative effects for specific components so that the effects of drug are impacted. Secondly, the intensity of the mechanical effect between the chitosan and the cross-linking agent is too weak to maintain the structure of the chitosan. Therefore, the produced drug carriers are in different shape. As a result, the effects of the drug carriers can't be accurately predicted when used in living bodies. Briefly speaking, although the electrospinning technology has simplest manufacturing process and best effects among the conventional drug carrier manufacturing technologies, some bottlenecks of manufacturing process still exist. Therefore, it is desired to improve the electrospinning technology.